Aging of skin such as skin wrinkle, sagging and loose skin, pigmentation, depigmentation, skin thinning, decrease of skin viscoelasticity, etc. influences seriously the quality of life (QOL) particularly in women, and when the degree is severe, it sometimes becomes an obstacle in social life. Conventionally, most of aging of skin was thought to be a so-called physiological aging which progresses with increasing age. However, recently, it is thought that almost all aging of skin is caused by aging due to exposure to ultraviolet rays (so-called photoaging). When skin is exposed to ultraviolet rays, mechanisms including inflammation, followed by disruption of dermal tissues and functional decrease of fibroblast cells are induced, and aging of skin such as described in the above progress.
On the other hand, similarly to aging of skin, scars of skin such as hypertrophic scars and keloid etc., also greatly influence the QOL of the patient, and it sometimes becomes an obstacle in social life depending on the degree or site (face, etc.) of the scar. Scars are generated during the healing process of following injury, etc. Specifically, when skin is damaged by injuries generated by surgery, etc., wound healing mechanisms such as hemorrhagic phase and coagulation phase, inflammatory phase, proliferating phase, etc. function, and epidermalization ends after a certain period. Then, the wound is healed with scar remaining after a maturation phase during which scar matures. At that time, depending on conditions such as delayed healing, patient's age and body sites, etc. the wound may form scars such as hypertrophic scar, scar contracture, keloid, atrophic scar, etc. In many cases, changes in thickness calm down with the passage of time, while symptoms such as reddening, pruritus, colic pain, etc. are severe in some cases, and the QOL of the patient can be significantly lowered for a long period of time. Further, wide scar or atrophic scar often remains even when the changes are calmed down, and the QOL of the patient was lowered for a long period of time in any of the cases.
As stated in the above, it can be said that aging of skin and scar of skin are not only cosmetic and functional problems of the patient but social problems such as QOL of the patient, etc. Therefore, many attempts for preventing and treating aging of skin and scars of skin have been made. Concerning prevention and treatment of aging of skin, for example, Patent Document 1 discloses that wrinkles and sagging skin are treated by applying externally a skin care product comprising basic fibroblast growth factor (bFGF) as active ingredient to the skin. bFGF is one kind of growth factor that has been found and identified by Grotendorst et al., which is a single chain polypeptide without sugar, having a molecular weight of about 17 K Dalton, and having a phospholipid affinity. Further, Patent Document 2 describes that an external preparation for skin comprising a fibroblast growth factor and epidermis growth factor exhibits an effect on improving wrinkles, pigmented spots, hair loss, etc. However, neither of the above-mentioned skin care product nor skin external preparation could prevent and treat aging of skin sufficiently.
On the other hand, the treatment of scar of skin has been conventionally based on surgical therapy. Therapeutic methods such as external use and topical administration of adrenal corticosteroid, application of adrenal corticosteroid-containing patch, parenteral use of anti-allergic agent, radiotherapy, etc. have been applied in some cases. However, these therapeutic methods require quite a long time period, and even by utilizing all of the therapeutic methods, it was difficult to treat sufficiently the scars. On the other hand, concerning the prevention of scars of skin, for example, Patent Document 3 discloses that when administering subcutaneously a basic fibroblast growth factor (bFGF) additionally to a hepatocyte growth factor (HGF) to the skin just after the wound is formed, tissue regeneration in the wound site is promoted, or formation of scars after the healing of wound is suppressed. The Patent Document 3 describes that in the mechanism of action, it is estimated that, first, the wounded healing action of bFGF functions during the early phase of injury, and then, during the scar maturation phase, HGF acts to suppress excessive growth and fibrosis of granulation tissue. However, effect of bFGF without being combined with HGF when a scar has already been formed has not been reported yet.
Further, Patent Document 4 discloses a pharmaceutical composition or veterinary composition for preventing and healing or treating organic diseases causing pathological and histological changes in vivo tissues, comprising ginsenoisides or their metabolic products, or salt thereof. In the section of “Prior Art” in Patent Document 4, it is described as follows: “Conventionally, it was known that topical application or topical spraying of basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) promotes partially the regeneration and reassembly of skin tissues, and exerts an effect and efficacy to skin ulcer and pressure sore. However, it cannot be said that the effect is satisfactory, even from a clinical standpoint (Singer, A. J. and Clark, R. A. F. New Eng. J. Med., 341, 738-746, 1999). Further, the aforementioned peptide factors (bFGF, PDGF) are pharmaceutical compositions that can be used only for topical application and topical spraying, and almost no effect or efficacy can be expected from a systemic administration such as intravenous administration.”
Under such circumstances, an agent for preventing and treating skin aging, or an agent for treating skin scars that can exert sufficient effect was awaited.
Patent Document 1: Japanese Laid-Open Patent Application No. 5-434442
Patent Document 2: Japanese Laid-Open Patent Application No. 2004-043313
Patent Document 3: Japanese Laid-Open Patent Application No. 2003-342194
Patent Document 4: Japanese Laid-Open Patent Application No. 2002-249498